Deep nasal sinus cavity microbiota dysbiosis in Parkinson\u2019s disease

Gian Pal,Mahboobeh Mahdavinia,Ali Keshavarzian,Ankur Naqib,Phillip A Engen,Christopher B Forsyth,Vivian Ramirez,Pete S Batra,Bobby A Tajudeen,Stefan J Green

doi:10.1038/s41531-021-00254-y

Gian Pal, Mahboobeh Mahdavinia + Show 8 more

Open Access

https://doi.org/10.1038/s41531-021-00254-y

Copy DOI

Abstract

Olfactory dysfunction is a pre-motor symptom of Parkinson’s disease (PD) that appears years prior to diagnosis and can affect quality of life in PD. Changes in microbiota community in deep nasal cavity near the olfactory bulb may trigger the olfactory bulb-mediated neuroinflammatory cascade and eventual dopamine loss in PD. To determine if the deep nasal cavity microbiota of PD is significantly altered in comparison to healthy controls, we characterized the microbiota of the deep nasal cavity using 16S rRNA gene amplicon sequencing in PD subjects and compared it to that of spousal and non-spousal healthy controls. Correlations between microbial taxa and PD symptom severity were also explored. Olfactory microbial communities of PD individuals were more similar to those of their spousal controls than to non-household controls. In direct comparison of PD and spousal controls and of PD and non-spousal controls, significantly differently abundant taxa were identified, and this included increased relative abundance of putative opportunistic-pathobiont species such as Moraxella catarrhalis. M. catarrhalis was also significantly correlated with more severe motor scores in PD subjects. This proof-of-concept study provides evidence that potential pathobionts are detected in the olfactory bulb and that a subset of changes in the PD microbiota community could be a consequence of unique environmental factors associated with PD living. We hypothesize that an altered deep nasal microbiota, characterized by a putative pro-inflammatory microbial community, could trigger neuroinflammation in PD.

Highlights

Parkinson’s disease (PD) is a complex neurodegenerative disease characterized by nigrostriatal degeneration resulting in bradykinesia, rigidity, tremor, and gait dysfunction[1]
Nasal microbial communities differed between random HC (rHC) and PD subjects, and this manifested at taxonomic levels of genus and species, but not phylum (Fig. 1a, b; Supplementary Tables 2, 3)
PD subjects aureus, and Staphylococcus epidermidis, and between Corynebac-We investigated whether clinical characteristics like age, PD duration, motor symptom severity (MDS-UPDRS, Hoehn & Yahr (H&Y)), olfactory terium striatum, Corynebacterium tuberculostearicum, and Peptoniphilus asaccharolyticus (Fig. 4)

Summary

Introduction

Parkinson’s disease (PD) is a complex neurodegenerative disease characterized by nigrostriatal degeneration resulting in bradykinesia, rigidity, tremor, and gait dysfunction[1]. Non-motor symptoms are typically present, including depression, constipation, and alteration of smell. Diminished sense of smell (hyposmia), is a common hallmark of prodromal PD2. PD gut dysbiosis is characterized by increased putative pro-inflammatory microbes, belonging to the phylum Proteobacteria, and a reduction in putative beneficial short chain fatty acids (SCFAs)-producing bacteria (e.g., bacteria from the genera Blautia, Roseburia, and Faecalibacterium)[3]. This gut dysbiosis may contribute to systemic and neuroinflammation, possibly leading to alphasynuclein misfolding and aggregation that is observed in PD intestinal and brain tissue[4,5]

Objectives

Methods

Results

Conclusion